title: Priming of the vascular endothelial growth factor signaling pathway by thrombospondin-1, CD36, and spleen tyrosine kinase.
abstract: CD36 plays a critical role in the inhibition of angiogenesis through binding to the type 1 repeats of thrombospondin-1 (TSP-1) and activating Fyn tyrosine kinase and MAPK pathways. Here, we reveal a novel association of CD36 with VEGFR-2 and spleen tyrosine kinase (Syk). We also address the correlation between the expression of CD36 and Syk by demonstrating that overexpression of CD36 in HUVECs up-regulates endogenous Syk expression. We also define a new role for TSP-1 and CD36 in the activation of the VEGFR-2 signaling pathway that requires Syk. Our findings also identify a role for Syk as a stimulator of VEGF-A-induced angiogenesis by increasing phosphorylation of Y1175 in VEGFR-2, which is a major tyrosine for promoting VEGF-A-induced endothelial cell migration. Together, these studies introduce a new signaling pathway for TSP-1, CD36, and Syk, and address the role of these proteins in regulating the angiogenic switch.
authors.affiliation: Division of Experimental Pathology, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Shideh
authors.initials: S
authors.lastname: Kazerounian
authors.forename: Mark
authors.initials: M
authors.lastname: Duquette
authors.forename: Millys A
authors.initials: MA
authors.lastname: Reyes
authors.forename: James T
authors.initials: JT
authors.lastname: Lawler
authors.forename: Keli
authors.initials: K
authors.lastname: Song
authors.forename: Carole
authors.initials: C
authors.lastname: Perruzzi
authors.forename: Luca
authors.initials: L
authors.lastname: Primo
authors.forename: Roya
authors.initials: R
authors.lastname: Khosravi-Far
authors.forename: Federico
authors.initials: F
authors.lastname: Bussolino
authors.forename: Isaac
authors.initials: I
authors.lastname: Rabinovitz
authors.forename: Jack
authors.initials: J
authors.lastname: Lawler
mesh_terms: D018955:CD36 Antigens / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000072377:Syk Kinase; D019700:Thrombospondin 1 / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D019700:Thrombospondin 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011505:Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; C000606896:SYK protein, human; D000072377:Syk Kinase